Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

Hoang Nam Vu; Kim, Ji Young; Hassan, Ahmed H. E.; Choi, Kihang; Park, Jong-Hyun; Park, Ki Duk; Lee, Jae Kyun; Pae, Ae Nim; Choo, Hyunah; Min, Sun-Joon; Cho, Yong Seo

doi:10.1016/j.bmcl.2015.11.012

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Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

Hoang Nam Vu;
Kim, Ji Young;
Hassan, Ahmed H. E.;
Choi, Kihang;
Park, Jong-Hyun;
외 6명

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9

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10

초록

We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well. (C) 2015 Elsevier Ltd. All rights reserved.

키워드

Metabotropic glutamate receptor; Antagonist; Picolinamides; Thiazole-2-carboxamides; Molecular docking; NEGATIVE ALLOSTERIC MODULATORS; GASTROESOPHAGEAL-REFLUX DISEASE; FRAGILE-X-SYNDROME; NEUROPATHIC PAIN; PHARMACOLOGY; MGLU(5); RATS; IDENTIFICATION; SYMPTOMS; EXPOSURE

제목: Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

저자: Hoang Nam Vu; Kim, Ji Young; Hassan, Ahmed H. E.; Choi, Kihang; Park, Jong-Hyun; Park, Ki Duk; Lee, Jae Kyun; Pae, Ae Nim; Choo, Hyunah; Min, Sun-Joon; Cho, Yong Seo

DOI: 10.1016/j.bmcl.2015.11.012

발행일: 2016-01-01

유형: Article

저널명: Bioorganic & Medicinal Chemistry Letters

권: 26

호: 1

페이지: 140 ~ 144